Fibrolase, an active thrombolytic enzyme in arterial and venous thrombosis model systems.

Abstract

Pharmacologic dissolution of an established thrombus has become an accepted therapeutic approach for many patients who develop thrombotic occlusive disease (1). Intravenous infusion of plasminogen activators, including recombinant tissue plasminogen activator (rt-PA), urokinase (UK), streptokinase (SK), and anisoylated plasminogen streptokinase-activator complex (APSAC), is effective in restoring blood flow in occluded arteries and veins (1,2). SK, APSAC, and UK activate circulating plasminogen as well as fibrin-bound plasminogen within the thrombus. The widespread systemic activation of the fibrinolytic system, leads to the depletion of α2-antiplasmin (α2-AP), and generation of free plasmin that degrades several plasma proteins, including fibrinogen, and factors V and VIII. On the other hand, rt-PA and recombinant single-chain urokinase-type plasminogen activator (scu-PA), activate plasminogen preferentially on the fibrin surface, where the fibrin associated plasmin is protected from rapid inactivation by α2-AP. Despite the availability of fibrin-specific thrombolytic agents, currently available therapy has a number of important limitations. A significant percentage (25–30%) of patients with acute myocardial infarction are resistant to reperfusion within 90 minutes despite the use of the most potent thrombolytic agents or combinations (3) and systemic fibrinogenolysis with accompanying bleeding is encountered frequently (4). Further, 10–30% of patients experience acute coronary reocclusion following thrombolytic therapy (5). There is also a small but significant risk of neurological complications (6) including stroke (7) and intracranial hemorrhage (8). Additionally, there is concern about the rapidly acting plasma inhibitor of t-PA, PAI-1 (9), which is significantly increased in myocardial infarction (10), and may, with other factors, predispose patients to reinfarction (11).KeywordsHigh Performance Liquid ChromatographyBlood Flow VelocitySnake VenomThrombolytic AgentFibrinolytic EnzymeThese keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.